Pregnancy 5 Years After Onset of Amyotrophic Lateral Sclerosis Symptoms: A Case Report and Review of the Literature.

BACKGROUND: Pregnancy in patients with amyotrophic lateral sclerosis (ALS) is extremely rare and often results in delivery of a healthy baby when patients are in the early stages of the disease. CASE: This report describes the case of a successful pregnancy 5 years after ALS onset. Significant worsening of weakness, unsteady balance, and dysphagia were noticed around the third trimester. A healthy child was delivered at term by planned Caesarean section. After delivery the patient developed remarkable weakness, dysphagia, and dysarthria. CONCLUSION: A literature search found 22 cases through PubMed and Ovid, with key words "amyotrophic lateral sclerosis" and "pregnancy." Both slow progression and rapid progression of ALS during pregnancy have been reported. Worsening of symptoms seems to be common, but little is still known about the influence of pregnancy on ALS onset and progression.

Longitudinal evaluation of uterine perfusion, endothelial function and central blood flow in early onset pre-eclampsia.

OBJECTIVES: Physiopathological mechanisms that trigger clinical manifestations in pre-eclampsia (PE) remain unclear, and management is still a challenge. The identification of tools to predict the onset of the disease and prevent its complications is of great interest in medical practice. The present study aims to evaluate uterine perfusion, endothelial function and central nervous system blood flow in pregnant women with high-risk factors for PE, for comparison of the results between the group of patients who developed early onset PE and those who remained normotensive throughout pregnancy. STUDY DESIGN: Sixty-two patients were recruited from our high-risk prenatal service, and followed throughout gestation. Patients were submitted to flow-mediated dilation, Dopplervelocimetry of uterine arteries and Dopplervelocimetry of ophthalmic arteries at three distinct moments of pregnancy: between 16+0 and 19+6weeks, between 24+0 and 27+6weeks and at hospital admission to delivery. MAIN OUTCOME MEASURES: Pulsatility index of uterine arteries, flow-mediated dilation and ophthalmic arteries resistance index were evaluated and compared between the two groups of patients. RESULTS: Ten pregnancies were complicated by early onset PE, and these patients presented a significantly higher pulsatility index of uterine arteries between 16+0 and 19+6weeks of gestation, compared with the normotensive group (p=0,016). Both flow-mediated dilation and ophthalmic arteries resistance index values were lower in affected patients at 24+0 to 27+6weeks (p=0,001), and by the time of delivery (p<0,002). CONCLUSIONS: Those findings suggest that impaired placental perfusion, endothelial dysfunction and central hyperperfusion temporarily precede the clinical manifestations of early onset pre-eclampsia.

Papel do Doppler do ducto venoso na restrição de crescimento intrauterino / Ductus venosus Doppler assessment in intrauterine growth restriction

Objetivo: O crescimento intrauterino restrito (CIUR) por insuficiência placentária persiste como grande desafio obstétrico. A interrupção da gestação representa a única estratégia de condução e baseia-se na predição de desfechos adversos. O Doppler tem valor reconhecido na avaliação seriada das alterações circulatórias nesses fetos, em geral sequenciais e proporcionais à gravidade do insulto hipóxico. Este estudo objetiva revisar as evidências do papel do Doppler de ducto venoso (DV) na predição de morbimortalidade perinatal em gestações complicadas por CIUR placentário grave e precoce. Métodos: Realizou-se revisão narrativa, com busca de artigos publicados nos últimos 10 anos nas bases Medline/PubMed, Lilacs e Scielo, sendo encontradas 132 referências. Pesquisas com animais e gestações múltiplas foram excluídas. Dos 115 artigos selecionados, 34 foram excluídos por inadequação ao tema. A revisão baseou-se nas demais 81 referências, além de trabalhos de reconhecida relevância no tema. Resultados: Estudos demonstram evidência consistente do papel do Doppler de DV na avaliação de fetos com CIUR, com bom valor preditivo para acidemia fetal e desfecho perinatal adverso. As principais estratégias de monitorização se baseiam na combinação do Doppler de vasos arteriais/venosos e parâmetros biofísicos, mas o Doppler de DV seria o melhor parâmetro isolado para predição de comprometimento fetal grave. Conclusão: A incorporação do Doppler de DV na monitorização de fetos com CIUR grave e precoce é capaz de predizer desfechos perinatais críticos. A avaliação de múltiplos vasos fetais parece aumentar a acurácia, porém não há evidência para embasar a definição de protocolos para o manejo clínico.(AU)

Objective: Intrauterine growth restriction (IUGR) due to early onset placental insufficiency remains to be a great challenge in obstetrical practice. Delivery is still the only available strategy of management, and timing such intervention depends on prediction of adverse outcomes. Dopplervelocimetry studies have recognized value in the evaluation of the sequential hemodynamic changes that are stablished in the arterial and venous circulation of these fetuses, which correlate with the severity of hypoxemic insult. This study aims to review evidence on ductus venosus (DV) Doppler`s role as a predictor of perinatal outcome in pregnancies complicated by severe early onset IUGR. Methods: A Medline/PubMed, Lilacs and Scielo search was performed to identify original articles and systematic reviews published in the last 10 years. Eighty-one references were included in this review, in addition to other papers of recognized relevance in the subject. Results: Studies demonstrate consistent evidence on DV Doppler`s role in the longitudinal evaluation of IUGR fetuses, with adequate predictive value for fetal acidemia and adverse outcome. Monitoring strategies are usually based on a combination of arterial and venous Doppler assessment, in addition to biophysical parameters, but DV Doppler seems to be the best single parameter for prediction of severe fetal compromise. Conclusion: Monitoring of fetuses with severe early-onset IUGR through DV Doppler is able to predict critical perinatal outcomes. Evaluation of multiple fetal vessels seems to increase accuracy of prediction, but to this moment there is not enough evidence to recommend protocols of management.(AU)

Função endotelial e perfusão uterina e em gestações subsequentementecomplicadas por pré-eclâmpsia / Endothelial function and uterine perfusion in subsequentpregnancies complicated by preeclampsia

Introdução: a fisiopatologia da pré-eclâmpsia (PE) baseia-se em deficiência no processo de placentação, associada à disfunção endotelial sistêmica materna. A investigação da ocorrência desses fenômenos, antes do aparecimento das manifestações clínicas da PE, pode constituir-se em novo método propedêutico para sua predição. Objetivos: comparar o processo de placentação e a função endotelial de gestantes de alto risco para desenvolvimento de PE, correlacionando esses achados com o seu desenvolvimento posterior. Pacientes e métodos: 74 gestantesforam submetidas ao exame de dilatação fluxomediada (DFM) da artéria braquial e dopplerfluxometria das artérias uterinas para avaliação da função endotelial e do processo de placentação, respectivamente. Os exames foram realizados entre 16 e 20 semanas de gestação e as pacientes foram acompanhadas até o puerpério.Resultados: 15 pacientes tiveram a gestação complicada por PE e 59 mantiveram-se normotensas até o puerpério. Pacientes que subsequentemente desenvolveram PE apresentaram, entre 16 e 20 semanas de gestação, maiores valores no índice de pulsatilidade das artérias uterinas (p<0,001), mas a análise da DFM não apresentoudiferença em relação às pacientes que se mantiveram normotensas. Conclusão:os dados observados sugerem que a deficiência no processo de placentação precede cronologicamente as manifestações clínicas de PE, o que não ocorre com a disfunção endotelial.

Introduction: the pathophysiology of preeclampsia (PE) is based on a deficiency in the process of placentation associated with systemic maternal endothelial dysfunction. The investigation on the occurrence of these phenomena before the onset of PE clinical manifestations can become a new diagnostic method for its prediction. Objectives:to compare the process of placentation and endothelial function in pregnant women athigh-risk for PE development, correlating these findings with its further development. Patients and methods: 74 pregnant women underwent flow-mediated dilation (DFM) of the brachial artery and Doppler flowmetry of uterine arteries to assess endothelial function and placentation process, respectively. The examinations were performedbetween 16 and 20 weeks of gestation and patients were followed until the postpartum period. Results: 15 patients had pregnancies complicated by PE and 59 remained normotensive until the postpartum period. Patients who subsequently developed PE presented high values of pulsatility index in uterine arteries (p <0.001), between 16 and 20 weeks gestation, however, the analysis of DFM did not show difference compared to patients who remained normotensive.Conclusion: The observed data suggest that deficiency in the placentation process chronologically precedes the clinical manifestations of PE, which does not occurwith endothelial dysfunction.

[Early-onset preeclampsia: is it a better classification for maternal and perinatal outcomes?]. / Pré-eclâmpsia precoce e tardia: uma classificação mais adequada para o prognóstico materno e perinatal?

PURPOSE: to evaluate the differences between the maternal and perinatal outcomes of pregnancies complicated by preeclampsia, according to the classification as the severe/mild form, and the early/late onset form. METHODS: a retrospective study with 211 pregnancies complicated by preeclampsia, assessed at a university reference center from 2000 to 2010. The diagnosis and disease severity were based on the values of blood pressure, proteinuria, and clinical and laboratory findings. The pregnant's age, skin color, parity, blood pressure, urine protein semiquantitative values, presence of bilateral notch in the uterine artery dopplervelocimetry and birth conditions were compared between patients with mild and severe disease, as well as between those of early/late onset. The disease was considered to be of early onset when diagnosed at less than 34 weeks of gestational age. RESULTS: most patients had the severe form of preeclampsia (82.8%), and the onset of the condition was early in 50.7%. Blood pressure values (133.6 ± 14.8 versus 115.4 mmHg, p=0.0004 and 132.2 ± 16.5 versus 125.7 mmHg, p=0.0004) and semiquantitative proteinuria (p=0.0003 and p=0.0005) were higher in the early and severe forms compared to mild and late forms. Infant birth weight (1,435.4 ± 521.6 versus 2,710 ± 605.0 g, 1,923.7 ± 807.9 versus 2,415.0 ± 925.0 g, p<0.0001 for both) and Apgar score (p=0.01 for both) were smaller for severe and early preeclampsia compared to mild and late preeclampsia. On the other hand, the presence of a bilateral notch in the uterine arteries was linked to the forms of early onset (69.2 versus 47.9%, p=0.02), whereas fetal growth restriction was more frequent in the severe forms of preeclampsia (30 versus 4.4%, p=0.008). CONCLUSION: the preeclampsia classification based on maternal clinical parameters better reflected the conditions of fetal nutrition, while the early onset of the condition was associated with placental vasculopathy detected by dopplervelocimetry.

Óxido nítrico e arginina di-metil assimétrica: possível via de explicação para o trabalho de parto pré-termo / Nitric oxide and asymmetric dimethyl arginine: a novel pathway to explain preterm labor

O trabalho de parto pré-termo (TPPT) assim como as outras causas de prematuridade respondem pela maior parcela da mortalidade e morbidade neonatal no mundo. Várias vias metabólicas já foram estudadas e diversas alterações já foram encontradas em pacientes que desenvolve TPPT. A via metabólica do óxido nítrico (NO) é reconhecida como um dos possíveis mecanismos de desencadeamento fisiopatológico do TPPT. Níveis elevados de dimetil-arginina assimétrica (ADMA), substância endógena inibidora da NO sintetase, estão relacionados com o desencadeamento de TPPT e com maiores taxas de complicações neonatais. O presente estudo aborda as evidências sobre a relação do TPPT e ADMA e as possíveis aplicações clínicas dessa associação.(AU)

Pre-term labor (PTL), as well as the other causes of prematurity, account for the largest portion of neonatal mortality and morbidity in the world. Several metabolic pathways were studied and a significative number of impairments have already been found in patients who develop PTL. The metabolic pathway of nitric oxide (NO) is recognized as one of the possible mechanisms of pathophysiological PTL?s trigger. High levels of asymmetric dimethyl arginine (ADMA), endogenous inhibitory substance of NO synthetase, are related to the triggering of PTL and with higher rates of neonatal complications. The present study addresses the evidence on the relationship of PTL and ADMA and possible clinical applications of this association.(AU)

Função endotelial e perfusão uterina e em gestações subsequentemente complicadas por pré-eclâmpsia / Endothelial function and uterine perfusion and subsequent pregnancies complicated by preeclampsia

Introdução: a fisiopatologia da pré-eclâmpsia (PE) baseia-se em deficiência no processo de placentação, associada à disfunção endotelial sistêmica materna. É preciso investigar a ocorrência desses fenômenos antes do aparecimento das manifestações clínicas da PE, considerando a disponibilidade de novos métodos propedêuticos de sua predição. Objetivos: comparar o processo de placentação e a função endotelial de gestantes de alto risco e os correlacionar com o desenvolvimento ou não da PE. Pacientes e métodos: 74 gestantes foram submetidas à dilatação fluxomediada (DFM) da artéria braquial e dopplerfluxometria de artérias uterinas para avaliação da função endotelial e do processo de placentação, respectivamente; entre 16 e 20 semanas de gestação e acompanhadas até o puerpério. Resultados: 15 pacientes tiveram a gestação complicada por PE e 59 mantiveram-se normotensas até o puerpério. Pacientes que subsequentemente desenvolveram PE apresentaram, entre 16 e 20 semanas de gestação, elevados valores no índice de pulsatilidade das artérias uterinas (p<0,001), mas a análise da DFM não apresentou diferença em relação às pacientes que se mantiveram normotensas. Conclusão: os dados sugerem que a deficiência no processo de placentação precede cronologicamente as manifestações clínicas de PE, o que não ocorre com a disfunção endotelial.

Introduction: the pathophysiology of pre-eclampsia (PE) is based on a deficiency in the placenta formation process, associated to systemic maternal endothelial dysfunction. The occurrence of these phenomena before the appearance of the clinical manifestations of PE should be investigated, considering that new propaedeutic methods are availablefor prediction. Objective: to compare placenta formation process and endothelial function of high-risk pregnant women and correlate them with the occurrence of PE. Patients and methods: 74 pregnant women were subjected to flow mediated dilation (FMD) of the brachial artery and Doppler flux of uterine arteries to assess the endothelial function and the placenta formation process, respectively, between the 16th and 20th gestation weeks and followed until the puerperal period. Results: 15 patients had their pregnancies complicated by PE while 59 remained normotensive until the puerperium. Patients who subsequently developed PE showed, between gestation weeks 16 and 20, high scores in the pulsatility index for uterine arteries (p<0.001), but the FDM analysis presented no difference in relation to the patients who continued normotensive. Conclusion: data suggest that deficiencies in the placenta formation process chronologically precedes the clinical manifestation of PE, which does not occur with endothelial dysfunction.

Pré-eclâmpsia precoce e tardia: uma classificação mais adequada para o prognóstico materno e perinatal? / Early-onset preeclampsia: is it a better classification for maternal and perinatal outcomes?

OBJETIVO: avaliar as diferenças entre o resultado materno e perinatal de gestações complicadas pela pré-eclâmpsia, segundo classificação em sua forma grave/leve e de início precoce/tardio. MÉTODOS: estudo retrospectivo envolvendo 211 gestações complicadas pela pré-eclâmpsia, avaliadas em centro universitário de referência, no período de 2000 a 2010. O diagnóstico e a gravidade da doença foram baseados nos valores da pressão arterial, proteinúria e nos achados clínicos e laboratoriais. A idade da gestante, cor da pele, paridade, pressão arterial, valores de proteinúria semiquantitativa, presença de incisura bilateral em artérias uterinas à doplervelocimetria e as condições de nascimento foram comparados entre os casos de forma leve/grave, assim como entre aqueles de surgimento precoce/tardio. A doença foi considerada precoce quando diagnosticada antes da 34ª semana. RESULTADOS: a maioria das gestantes apresentava a forma grave da pré-eclâmpsia (82,8 por cento) e 50,7 por cento, de início precoce. Os valores da pressão arterial (133,6±14,8 versus 115,4 mmHg, p=0,0004, e 132,2±16,5 versus 125,7 mmHg, p=0,0004) e proteinúria semiquantitativa (p=0,0003 e p=0,0005) foram mais elevados nas formas grave e precoce em relação às formas leve e tardia. O peso ao nascimento (1.435,4±521,6 versus 2.710±605,0 g, 1.923,7±807,9 versus 2.415,0±925,0 g, p<0,0001 para ambos) e o índice de Apgar (p=0,01 para ambos) foram menores nas formas grave e precoce da pré-eclâmpsia, em relação às formas leve e tardia. Por outro lado, a presença de incisura bilateral em artérias uterinas se associou às formas de início precoce (69,2 versus 47,9 por cento, p=0,02), enquanto a restrição de crescimento fetal foi mais frequente nas formas graves da pré-eclâmpsia (30 versus 4,4 por cento, p=0,008). CONCLUSÃO: a classificação da pré-eclâmpsia baseada em parâmetros clínicos maternos refletiu melhor as condições de nutrição fetal, enquanto o seu surgimento precoce se associou melhor à vasculopatia placentária detectada à doplervelocimetria.

PURPOSE: to evaluate the differences between the maternal and perinatal outcomes of pregnancies complicated by preeclampsia, according to the classification as the severe/mild form, and the early/late onset form. METHODS: a retrospective study with 211 pregnancies complicated by preeclampsia, assessed at a university reference center from 2000 to 2010. The diagnosis and disease severity were based on the values of blood pressure, proteinuria, and clinical and laboratory findings. The pregnant's age, skin color, parity, blood pressure, urine protein semiquantitative values, presence of bilateral notch in the uterine artery dopplervelocimetry and birth conditions were compared between patients with mild and severe disease, as well as between those of early/late onset. The disease was considered to be of early onset when diagnosed at less than 34 weeks of gestational age. RESULTS: most patients had the severe form of preeclampsia (82.8 percent), and the onset of the condition was early in 50.7 percent. Blood pressure values (133.6±14.8 versus 115.4 mmHg, p=0.0004 and 132.2±16.5 versus 125.7 mmHg, p=0.0004) and semiquantitative proteinuria (p=0.0003 and p=0.0005) were higher in the early and severe forms compared to mild and late forms. Infant birth weight (1,435.4±521.6 versus 2,710±605.0 g, 1,923.7±807.9 versus 2,415.0±925.0 g, p<0.0001 for both) and Apgar score (p=0.01 for both) were smaller for severe and early preeclampsia compared to mild and late preeclampsia. On the other hand, the presence of a bilateral notch in the uterine arteries was linked to the forms of early onset (69.2 versus 47.9 percent, p=0.02), whereas fetal growth restriction was more frequent in the severe forms of preeclampsia (30 versus 4.4 percent, p=0.008). CONCLUSION: the preeclampsia classification based on maternal clinical parameters better reflected the conditions of fetal nutrition, while the early onset of the condition was associated with placental vasculopathy detected by dopplervelocimetry.